Alzheimer's - Dementia, Author Interviews, Infections, Parkinson's / 22.09.2022

MedicalResearch.com Interview with: Jiangwei Sun PhD Postdoctoral researcher in Prof. Jonas Ludvigsson's group Department of Medical Epidemiology and Biostatistics Karolinska Institutet MedicalResearch.com: What is the background for this study? Response: A potential infectious etiology has been hypothesized for neurodegenerative diseases, as findings in animal studies have demonstrated that infectious processes might impact pathogenesis, phenotype, and progression of neurodegenerative disease. The extrapolation of such findings to a human context is however not straightforward. previous studies have mostly examined the role of specific pathogens on a specific neurodegenerative disease, e.g., herpesvirus for Alzheimer’s disease, and influenza, hepatitis C virus, and Helicobacter pylori for PD, with inconclusive results. Although several studies have also assessed associations between infectious diseases and risk of dementia and AD, influence of potential surveillance bias (greater-than-expected surveillance of disease after infections) and reverse causation (due to for example diagnostic delay of neurodegenerative diseases) on the associations was not always fully addressed. Therefore, whether infection is indeed a risk factor rather a comorbidity or secondary event of neurodegenerative disease remains unknown. In contrast to Alzheimer’s disease, and Parkinson’s disease, the potential link between infection and ALS has been less explored. (more…)
Author Interviews, Brigham & Women's - Harvard, Neurology, Parkinson's / 21.06.2022

MedicalResearch.com Interview with: Vikram Khurana, MD, PhD Chief of the Division of Movement Disorders Department of Neurology Brigham and Harvard Medical School Principal investigator, Ann Romney Center for Neurologic Diseases at the Brigham MedicalResearch.com:  What is the background for this study?   Response: Proteins abnormally accumulate in brain cells (neurons and glial cells) in all neurodegenerative diseases. In Parkinson’s disease and related disorders, the key protein that accumulates and aggregates is called “alpha-synuclein.” Presumably, when a protein like alpha-synuclein abnormally folds and aggregates, the abnormal form of the protein can become toxic to the neuron, eventually leading to cell death. Equally, the protein may no longer be able to carry out its normal function. This begs the question – what does alpha synuclein actually do? Most evidence to date points to alpha-synuclein being involved in the transport of other proteins and chemicals around the cell, by closely associating with vesicles that are small circular containers enclosed by fat (“lipid) membranes. But alpha-synuclein is not just found associated with these vesicle membrane. It is found away from the membrane and it’s been unclear what it does there. (more…)
Author Interviews, Genetic Research, Parkinson's / 06.05.2021

MedicalResearch.com Interview with: Clemens R. ScherzerClemens R. Scherzer, M.D. Center for Advanced Parkinson Research Harvard Medical School Brigham and Women’s Hospital Boston, MA MedicalResearch.com: What is the background for this study? Response: Parkinson's disease is the fastest growing brain disorder. The number of patients is projected to double to 14 million by 2040. The total cost of Parkinson's is $52 billion every year in the U.S. Yet, there are no medicines available to slow the disease. Current treatments temporarily alleviate symptoms, but do not address the underlying disease process, which continues to relentlessly progress. To begin to solve this puzzle, we searched the genome of 3,821 Parkinson's disease patients for genetic variants linked to rapid progression over time to dementia, which is a major determinant for a Parkinson's disease patient’s quality of life. These patients were deeply characterized in the International Genetics of Parkinson Disease Progression (IGPP) Consortium, a grass-roots, collaborative network of Parkinson’s investigators, with 31,578 longitudinal study visits over up to 12 years from disease onset.  (more…)
Author Interviews, Dermatology, JAMA, Parkinson's / 01.10.2020

MedicalResearch.com Interview with: Wenquan Zou, MD/PhD, Professor Department of Pathology Associate Director National Prion Disease Pathology Surveillance Center Case Western Reserve University School of Medicine Cleveland, Ohio 44106 MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. It is characterized by the accumulation of pathologically misfolded α-synuclein (αSynP) aggregates in the brain. Currently, a definite diagnosis relies on the detection of αSynP-containing Lewy bodies in the brain of PD patients. Development of a reliable and sensitive assay for αSynP in easily accessible peripheral tissue specimens is critical for early or differential diagnosis, determination of disease severity, and evaluation of therapeutic efficacy in clinical trials. Previous studies have revealed that the pathologically phosphorylated α-synuclein is detectable with traditional immunohistochemistry (IHC) and immunofluorescence (IF) microscopy but the sensitivity with IHC/IF is highly variable and inconsistent. Also the prion-like aggregation seeding activity of αSynP is detected in cerebrospinal fluid (CSF) of Parkinson’s disease patients with highly sensitive real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification assays (PMCA). But the lumbar puncture to collect CSF is more invasive compared to skin punch biopsy. (more…)
Author Interviews, Neurology, Parkinson's / 22.06.2020

MedicalResearch.com Interview with: Stewart A. Factor, D.O. Professor of Neurology Director of the Movement Disorders Program Vance Lanier Chair of Neurology Emory University School of Medicine MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by OFF episodes.  Response: Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease characterized by motor symptoms, including tremor at rest, rigidity and impaired movement, as well as significant non-motor symptoms, such as cognitive impairment, psychiatric symptoms and autonomic symptoms (i.e. urinary issues, constipation, low blood pressure). It is the second-most common neurodegenerative disease after Alzheimer’s disease and it is predicted that the prevalence of Parkinson’s disease will double by the year 2040. The symptoms of PD are in substantial part, due to loss of dopamine nerve cells in the brain. The current standard of care for PD includes replacing the dopamine loss by the use of oral carbidopa/levodopa. Levodopa is a precursor of dopamine, converted in the brain. OFF episodes have been a significant unmet need in Parkinson’s disease since the emergence of levodopa. Initially, levodopa controls PD symptoms in a continuous fashion throughout the day. With time the response becomes less predictable and patients experience a re-emergence or worsening of PD symptoms. These episodes are what we mean by OFF episodes. OFF episodes can be characterized, in part, by re-emergence of motor symptoms including tremor, stiffness or slowed movement that can happen at any point during the day. OFF episodes typically begin within the first five years of treatment and occur at the end of a dose. This is referred to as end of dose failure or wearing off. Within the first four to six years after diagnosis, regardless of disease severity, up to 60 percent of people with PD experience OFF episodes. With time these episodes become longer, more severe and disabling, more frequent and less predictable as PD progresses. They can take up more than half the day OFF episodes may alter a persons’ ability to perform everyday activities by slowing or even precluding their completion. The result is significant burden and distress for people living with Parkinson’s disease (PD) and their care partners. CTH-300 was a Phase 3, 12-week, randomized, double-blind, placebo-controlled, parallel group, study examining the efficacy, safety and tolerability of apomorphine hydrochloride sublingual film (KYNMOBI) in people with levodopa-responsive PD complicated by OFF episodes. The primary endpoint was a mean change in the score from pre-dose in the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination at 30 minutes after dosing at the 12-week visit of the maintenance treatment phase. The key secondary endpoint was the percentage of people with PD with a patient-rated full ON (or best) response within 30 minutes at the 12-week visit of the maintenance treatment phase. (more…)
Author Interviews, Neurological Disorders, Parkinson's / 15.04.2020

MedicalResearch.com Interview with: Dr. Viviane Labrie, PhD Dr. Labrie is an associate professor in Van Andel Institute’s Center for Neurodegenerative Science, where she studies Parkinson’s, Alzheimer’s and other neurological diseases. MedicalResearch.com: What is the background for this study? Response: One of the most puzzling and persistent mysteries in neuroscience has been why some people are “right-brained” while others are “left-brained.” The two sides of the brain have different jobs. The left side is analytic and problem-solving, while the right side manages creativity and artistic talents. But despite their differences, the two sides are composed of the same cell types — essentially, brain neurons and their support cells. In this study, we sought to understand how it is possible for these cells to behave completely differently depending on what hemisphere they’re located in.  We also wanted to examine the reasons behind asymmetry in Parkinson’s disease; that is, why Parkinson’s symptoms typically start on one side of the body before the other. This asymmetry in neurodegeneration and symptoms in patients is one of the biggest unsolved puzzles in the Parkinson’s disease field — why do brain cells in one hemisphere begin dying before brain cells in the other hemisphere? (more…)
Author Interviews, Depression, Exercise - Fitness, JAMA, Parkinson's / 10.04.2019

MedicalResearch.com Interview with: Dr. Jojo Kwok  R.N., BN(Hons), MPH, Ph.D. School of Nursing, Li Ka Shing Faculty of Medicine The University of Hong Kong MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Before the study, we knew that mind-body exercises such as yoga and stretching improves the physical health of patients with Parkinson’s disease (PD), however the benefits to their mental health was not known. This study concludes that mindfulness yoga alleviates psychological distress, improves spiritual well-being and quality of life, not to mention motor symptoms and mobility. When it comes to managing the stress and symptoms of Parkinson Disease, what is exciting, is that yoga has now been proven to be a better strategy than just stretching. Yoga draws together body, mind and spirit through mindful practice of 1) yoga posture, 2) breathing and 3) meditation. These form the three core components of our Mindfulness Yoga Program. Mindfulness is non-judgemental awareness of the present moment - of one’s physical sensations and thoughts, be they positive or negative. By adopting a mind-body approach, patients are much better positioned to reframe their illness journey than through physical training alone. By learning to relate non-judgmentally to their physical symptoms and emotions, they develop new coping skills that cultivate openness, acceptance and resilience to these symptoms. They feel better.  (more…)
Alzheimer's - Dementia, Author Interviews, Coffee, Parkinson's / 14.11.2018

MedicalResearch.com Interview with: Donald Weaver, PhD, MD, FRCPC, FCAHS Senior Scientist and Director, Research Institute Krembil Research Institute University Health Network Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: First, we are seeking novel molecules that might have usefulness in the treatment of Alzheimer’s disease (AD). Since Mother Nature is a superb chemist, natural products are an ideal place to start looking for possible therapeutics. There is a long history (penicillin, digitalis …) of drugs identified from natural product sources. Moreover, in earlier work by us, we have shown that other natural products extracted from maple syrup have possible therapeutic efficacy against AD. Therefore, it was logical for us to look at extracts of coffee. We see similarities between maple syrup and coffee. In both of these natural products, the plant derived material (i.e. the coffee bean, or sap from maple syrup) is initially boiled or roasted prior to its use; thus, it is not a direct simple plant product, but one that has been heated (boiled or roasted). We suspect that the heating process “does more chemistry” enabling the generation of new molecules from the plant derived materials. In our study we show that a class of compounds (phenylindanes) from roasted coffee has the ability to inhibit the misfolding of two proteins (beta-amyloid, tau) whose misfolding and aggregation (“clumping”) is implicated in the disease process of AD. Second, as described below, there is already epidemiological evidence that coffee consumption may offer some protective effects against Alzheimer’s disease and Parkinson’s disease (PD), so by looking at the constituents of coffee for chemicals that might block the clumping of beta-amyloid and/or tau, was an attempt to seek a molecular link explaining the epidemiology. (more…)
Author Interviews, Gastrointestinal Disease, Parkinson's / 01.11.2018

MedicalResearch.com Interview with: Viviane Labrie, Ph.D. Assistant Professor Center for Neurodegenerative Science Van Andel Research Institute Grand Rapids, Michigan MedicalResearch.com: What is the background for this study? Response: Our lab has an interest in the early events and initiation of neurodegenerative diseases. Parkinson’s disease for a long time was thought to be a movement disorder driven by the destruction of dopamine neurons in a specific area of the brain, the substantia nigra. In the last 10 years it has become evident that Parkinson’s disease is not just a movement disorder but hosts a whole range of non-motor systems. One of the most common non-motor symptoms in Parkinson’s patients is issues with the gastrointestinal (GI) tract. GI symptoms often occur early in Parkinson’s disease; for many patients, GI symptoms precede the onset of motor symptoms by as many as 2 decades. Moreover, the GI is not only involved in the early signs of Parkinson’s but has been proposed to be a place in the body where Parkinson’s disease begins. The hallmark pathology of Parkinson’s disease in the brain is Lewy bodies, which contains a clumped form of a protein called alpha-synuclein. There is evidence that Parkinson’s disease pathology, this clumped alpha-synuclein protein, is detectable in the GI tract, even many years before the onset of Parkinson’s motor symptoms. Clumped alpha-synuclein is also capable of traveling across nerve cells. There is evidence that clumped alpha-synuclein can travel up the nerve that connects the GI tract to the brain and enter the brain. This could be disastrous because clumped alpha-synuclein can seed and spread in the brain, which has neurotoxic effects and can eventually lead to Parkinson’s disease. In fact, in the brain of Parkinson’s patients, one of the first places where alpha-synuclein clumps are detected is at the terminal where the gut nerve connects to the brain, and this pathology advances from this point to other brain areas as the disease progresses. This intriguing connection of the GI tract to the early processes of Parkinson’s disease had us interested in trying to understand how the gut could be involved in triggering Parkinson’s. But the GI tract is a very big place, and we first asked ourselves, where should we look to better understand GI involvement in Parkinson’s disease? (more…)
Author Interviews, JAMA, Neurology, Outcomes & Safety, Parkinson's, Pharmacology, University of Pennsylvania / 04.10.2018

MedicalResearch.com Interview with: Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by my own experiences as a neurologist-neuroscientist. I care for Parkinson disease patients, and over the year, have had numerous instances in which a person was taking a medication that could interact with their Parkinson disease medications, or could worsen their PD symptoms. (more…)
Author Interviews, Exercise - Fitness, JAMA, Neurology, Parkinson's / 23.09.2018

MedicalResearch.com Interview with: Fudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou 310058, ChinaFudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou  China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Parkinson disease (PD) is the second most common neurodegenerative disease affecting approximately 10 million people around the world. To date, the cause of PD remains poorly understood. It is reported that 90% PD cases have no identifiable genetic cause. What’s worse, few therapeutic advances for the treatment of PD have been made in the past decades. Nevertheless, growing prospective longitudinal studies shed lights on the potential beneficial effect of lifestyle factors on reducing the risk of developing Parkinson disease. In this study, we performed a a dose-response meta-analysis of more than half a million participants. We found that physical activity, particularly moderate to vigorous physical activity, could significantly reduce PD risk. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Parkinson's / 27.03.2018

MedicalResearch.com Interview with: Benjamin Dawson, B.Sc. MD Candidate 2020 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications - it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia. While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder ('acting out' the dreams at night). When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia. (more…)
Author Interviews, Parkinson's / 11.03.2018

MedicalResearch.com Interview with: Prof. Jeffrey Hausdorff PhD Director of the Center for the Study of Movement, Cognition and Mobility Full Professor in the Sackler School of Medicine and Sagol School of Neuroscience Tel Aviv Medical Center MedicalResearch.com: What is the background for this study?  Response: Many people with Parkinson’s disease suffer from a disturbing symptom referred to as “freezing of gait”. When freezing occurs, the person’s feet inexplicably become stuck to the floor and he or she is unable to move forward, despite efforts to walk. Initially, the problem can last just a few seconds and occur very infrequently. As the problem progresses, however, freezing can last many seconds, occurring frequently throughout the day. This can lead to a very frustrating situation that may also be dangerous. People with freezing of gait have an increased risk of falls and reduced health-related quality of life. The behavioral manifestation of freezing of gait is a problem with walking, i.e., it is a “motor” symptom. However, there is also evidence that deficits in specific aspects of cognitive function (i.e., executive function) may also contribute to freezing of gait. The goals of the present work were to use non-invasive brain stimulation to better understand if these cognitive deficits are indeed in the causal chain and if non-invasive brain stimulation that simultaneously targets both motor and cognitive brain areas that are believed to involved with freezing have a better impact on freezing and related symptoms than stimulation that targets only motor brain areas or sham stimulation. (more…)
Author Interviews, Genetic Research, JAMA, Neurology, Parkinson's / 25.01.2018

MedicalResearch.com Interview with: Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features. To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score. We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08). (more…)
Author Interviews, Parkinson's / 28.12.2017

MedicalResearch.com Interview with: Dr. Frances M. Weaver PhD Hines VA Hospital Center of Innovation for Complex Chronic Healthcare Hines, IL 60141 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Research has shown that deep brain stimulation (DBS) for Parkinson’s disease (PD) improves motor function and this improvement is sustained. There is also improvement in quality of life after DBS. However, it is not known whether DBS also effects survival. A few studies that have examined survival have had mixed results. In the current study we compared survival for a large cohort of persons with Parkinson’s disease who underwent DBS to a match group of persons with PD who were managed medically. We found a modest improvement in survival for persons with Parkinson’s disease who underwent DBS compared to individuals who did not. (more…)
Author Interviews, Parkinson's, Pharmacology / 14.12.2017

MedicalResearch.com Interview with: Dr. Youcef Mehellou PhD Lecturer in Medicinal Chemistry Cardiff School of Pharmacy and Pharmaceutical Sciences Cardiff University MedicalResearch.com: What is the background for this study? Response: Over the last decade or two, there has been many reports linking genetic mutations to the pathogenesis of Parkinson’s disease (PD). Among the proteins that have been found to be mutated in PD is a protein called PINK1. Indeed, PINK1 mutations that disturb its function in cells were found to be causal of PD in humans. Subsequent studies showed that PINK1 is a major player in maintaining healthy neurons. This is because it is one of the components involved in controlling the quality of the mitochondria, an organelle within the cell, and it does this by triggering the disposal of unhealthy mitochondria. Overall, studies into PINK1 indicated that the activation of PINK1 as a plausible strategy for maintaining health neurons and hence slowing down the development and progress of Parkinson’s disease. (more…)
Alzheimer's - Dementia, Author Interviews, Infections, Neurology, Parkinson's / 22.09.2017

MedicalResearch.com Interview with: Rima McLeod, M.D., F.A.C.P, F.I.D.S.A Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College, Director, Toxoplasmosis Center, Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis, Member Global Health Center, Affiliate CHeSS; Attending Physician, Chicago Medicine, The University of Chicago MedicalResearch.com: What is the background for this study? * One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. * Approximately fifteen million of these have congenital toxoplasmosis. * The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites. * In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process. * Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior. * Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases. * Although neurobehavioral disease is associated with seropositivity, causality is unproven. * Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality. * Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases. * We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design * To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments? * We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions. * To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  (more…)
Author Interviews, Diabetes, Lancet, Parkinson's / 08.08.2017

MedicalResearch.com Interview with: Dr Dilan Athauda MRCP Sobell Department of Motor Neuroscience and Movement Disorders UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery London MedicalResearch.com: What is the background for this study? Response: Exenatide is a synthetic version of a naturally occurring protein - exendin-4 - that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes. Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival. Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw. As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial. (more…)
Author Interviews, JAMA, Parkinson's / 15.06.2017

MedicalResearch.com Interview with: Rajesh Pahwa MD Department of Neurology University of Kansas Medical Center, Kansas City, KS, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia. This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017). (more…)
Author Interviews, Gastrointestinal Disease, Karolinski Institute, Parkinson's / 29.04.2017

MedicalResearch.com Interview with: Karin Wirdefeldt, MD, PhD Associate professor Karolinska Institutet Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: It has been hypothesized that Parkinson's disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson's disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected). (more…)
Author Interviews, Diabetes, Parkinson's, Science / 09.12.2016

MedicalResearch.com Interview with: Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The investigational drug at the heart of our study, MSDC-0160, has been in development to treat type 2 diabetes by improving cellular metabolism. In Parkinson’s, reductions in cellular metabolism slow down vital housekeeping processes that clear out toxic proteins that otherwise accumulate with age. If these proteins aren’t removed, they clump together, leading to the damage and cell death that causes Parkinson’s hallmark symptoms, such as rigidity and tremor. MSDC-0160 helps keep these housekeeping processes working, ultimately protecting the brain. We demonstrated that MSDC-0160 has strong, reproducible, positive effects across multiple models of Parkinson’s disease—it rescued dopamine-producing cells, improved behavioral deficits in mouse models and reversed inflammation. Overall, we believe it is a strong candidate for repurposing as a potential treatment that actually may slow the disease’s progression, rather than only mitigating symptoms. (more…)
Author Interviews, JAMA, Neurological Disorders, Parkinson's / 21.11.2016

MedicalResearch.com Interview with: Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias. Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease. (more…)
Author Interviews, Parkinson's, Pharmacology / 28.09.2016

MedicalResearch.com Interview with: Rosa & Co. LLC,Dr. Christina Friedrich Chief Engineer, PhysioPD Rosa & Co. LLC MedicalResearch.com: What is the background for this study? Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets. (more…)
Author Interviews, Biomarkers, JAMA, NIH, Parkinson's / 26.09.2016

MedicalResearch.com Interview with: Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls. (more…)
Alzheimer's - Dementia, Author Interviews, Chemotherapy, Parkinson's / 13.07.2016

MedicalResearch.com Interview with: Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated. Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer's Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau). (more…)
Alzheimer's - Dementia, Author Interviews, Brain Injury, JAMA, Parkinson's / 11.07.2016

MedicalResearch.com Interview with: Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington MedicalResearch.com: What is the background for this study? Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. This is bad enough for someone to deal with but it's made even worse if the head injury isn't even the victim's fault. Previous research has focused especially on Alzheimer's disease. A more limited research has focused on Parkinson's disease. We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer's and Parkinson's disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies. (more…)
Author Interviews, JAMA, MRI, Parkinson's / 06.07.2016

MedicalResearch.com Interview with: Blayne Welk, MD, MSc,FRCSC Assistant Professor of Surgery Western University London, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prior research has demonstrated that gadolinium, which may be used during MRI scans to help visualise the body organs, can be deposited in the body, and remain there for years. The US FDA released a notice last year stating that further research was needed to evaluate the clinical implications of these brain deposits. One of the areas that gadolinium is deposited is the brain, specifically in two regions which control voluntary movement (the globus pallidus and dentate nucleus). Damage to these areas could cause symptoms of Parkinsonism. We used administrative data from Ontario, Canada to evaluate whether people who underwent MRI scans with gadolinium had a higher risk of developing Parkinsonism in the future. In this study, we did not demonstrate an increased risk of Parkinsonism in patients exposed to gadolinium. (more…)
Author Interviews, Dermatology, JAMA, Parkinson's / 21.03.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes. Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells. Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson's disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson's disease. (more…)
Author Interviews, Frailty, Hip Fractures, Parkinson's, PLoS / 08.02.2016

MedicalResearch.com Interview with: Helena Nyström MD, PhD Candidate Department of Community Medicine and Rehabilitation Umeå University Umeå, Sweden Medical Research: What is the background for this study? Response: Parkinson’s disease (PD) has an insidious onset and the prodromal phase, preceding the onset of the characteristic PD symptoms, may last for decades. Most prodromal signs previously reported are of non-motor type, such as sleep and mood disorders. However, recent studies have reported balance problems and an increased risk of accidental injuries in the last 3-5 years before diagnosis of Parkinson’s disease , and in a previous study we found a lower muscle strength at military conscription in men who were diagnosed with  Parkinson’s disease three decades later. In this study, we aimed to investigate if such subtle strength deficits may translate into an increased risk of fall-related injuries. Medical Research: What are the main findings? Response: The median study time was 20 years before the diagnosis of  Parkinson’s disease , and during this time more individuals with PD (18%) than controls (11.5%) had at least one fall-related injury. The risk was most increased in the last few years before the diagnosis of  Parkinson’s disease , but a difference between the groups appeared already a decade before the PD diagnosis. The risk of hip fracture was increased during the entire study time of 26 years before the diagnosis of Parkinson’s disease . (more…)